The Core will carry out the technological development of novel infrared spectroscopies by improved methods of single frequency 2D IR its data acquisition and processing, modeling of isotopically substituted peptides including carbon-hydrogen modes and amide modes in beta sheets, haipins, soluble and membrane bound structures, tryptophan zippers and comparisons with molecular dynamics simulations. New techniques of 2D IR dual frequency and dual isotope replacement strategies will be further developed to obtain coupling of the C-H and C=O modes of glycophorin-A and other proteins in membrane bound configurations. The joint correlations of the frequencies of various modes will be found. Equilibrium and nonequilibrium dynamics methods of 2D IR will be applied to downhill folding proteins and to temperature and pH jump induced conformational changes. A sub-diffraction limit optical microscope will be constructed and applied to human plasma fibrinogen and lipid vesicles. The mechanism of protein translocation of cell penetrating peptides will be deduced. New IR designs of surface plasmon resonance combined with FTIR will be developed and used in folding experiments. 2D IR of the folding intermediates of the Villin headpiece will be recorded Collaborative projects using these technologies are planned on amyloid structures and multiplexing for Alzheimer'disease oligomers;2D IR spectroscopy of site-specific vibrations in proteins introduced by mutagenesis and side-chain modifications and by isotopomers;interferon-l measuring receptor engagement at the single cell level in real time by reflection fluorescence microscopy;tumor oxygenation by two-photon excited phosphorescence;novel cassettes for multiplexing signals from single molecules in cells;2D IR of trans membrane protein structures and dynamics;and engineering serpin de-polymerization by design. Service projects on chemosensors, multi-porphyrin arrays, NADH in trehalose, Chlamydomonas Centrin, self-assembly of a hairpin, tubule-based drug delivery, the mobility of allylamine, lateral transport of proteins and lipids in cell membranes and chemiluminescence light amplifiers of fluorescein-luminol are planned. Dissemination is planned through journal articles and reviews, Newsletters, a symposium on two dimensional spectroscopies besides regular seminars. We will train visiting faculty researchers, post-doctoral fellows, and graduate students in the applications of infrared spectroscopies to biological questions.